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- A fast responsive chromogenic and near-infrared fluorescence lighting-up probe for visual detection of toxic thiophenol in environmental water and living cellsPublication . Wu, Juanjuan; Su, Dongdong; Qin, Caiqin; Li, Wei; Rodrigues, João; Sheng, Ruilong; Zeng, LintaoThiophenols as high toxic environmental pollutants are poisonous for animals and aquatic organisms. Therefore, it is indispensable to monitor thiophenols in the environment. Herein, a novel near-infrared fluorescent probe was developed for the detection of thiophenols, which was easily prepared by one-step coupling of 2,4-dini trobenzenesulfonyl chloride with Nile blue. The probe showed a significant near infrared (∼675 nm) fluores cence “turn-on” response to thiophenols with some good features including chromogenic reaction, high sensi tivity and selectivity, fast response, near-infrared emission along with low detection limit (1.8 nM). The probe was employed to rapidly and visually determine thiophenols in several industrial wastewaters with good re coveries (90–110%). Moreover, this probe has been demonstrated good capability for imaging thiophenol in HeLa cells
- Chemical sensors towards environmental toxic molecule monitoring: fluorescent probes for detection of thiophenolPublication . Jiang, Lirong; Wu, Juanjuan; Min, Douyong; Rodrigues, João; Sheng, RuilongThiophenols, a family of important industrial chemicals, is highly toxic for aquatic organisms and human beings. Developing new chemical sensors with the merit of fast, low cost, portable, selective and sensitive, as well as visualizable signal output for efficient detection of thiophenols, is highly desirable. This spotlight article reviewed and discussed the current trend and statement of thiophenols-specific fluorescent probes. Moreover, the future outlook in this field was also stated.
- Green polymers toward nanobiotechnology(I): synthesis of glycopolypeptides and their analoguesPublication . Wang, Zhao; Neves, Ana Rute; Olim, Filipe; Tomás, Helena; Tang, Shi; Sheng, RuilongHarnessing natural-based renewable molecular resources to construct functional synthetic green polymers is a promising research frontier at the interface of sustainable/green chemistry, polymer chemistry and nanobiotechnology. As natural glycoprotein mimics/analogues and biocompatible building blocks of nanobio- materials, synthetic functional glycopolypeptides and their structural/functional analogues have attracted great attentions in recent years. This mini-perspective article reviewed current synthetic strategies and methods of glycopolypeptides and their analogues. The pros and cons of the synthesis protocols were discussed, moreover, possible future perspectives in this field were also stated.
- A selective cascade reaction-based probe for colorimetric and ratiometric fluorescence detection of benzoyl peroxide in food and living cellsPublication . Wu, Xiaoli; Zeng, Lintao; Chen, Bao-Quan; Zhang, Ming; Rodrigues, João; Sheng, Ruilong; Bao, Guang-MingA novel colorimetric and ratiometric fluorescent probe (Cou-BPO) was readily prepared for specific detection of harmful benzoyl peroxide (BPO). The probe Cou-BPO reacted with BPO via a selective oxidation cleavage-induced cascade reaction of the pinacol phenylboronate group, which resulted in an observable colorimetric and ratiometric fluorescence response towards BPO with a fast response time (o15 min) and a low detection limit (56 nM). For practical application, facile, portable and sensitive test paper of Cou-BPO has been prepared for visual detection of BPO. Furthermore, we employed Cou-BPO as a probe to determine BPO in food samples and living cells.
- Gene delivery using dendrimer-entrapped gold nanoparticles as nonviral vectorsPublication . Shan, Yuebin; Luo, Ting; Peng, Chen; Sheng, Ruilong; Cao, Amin; Cao, Xueyan; Shen, Mingwu; Guo, Rui; Tomás, Helena; Shi, XiangyangDevelopment of highly efficient nonviral gene delivery vectors still remains a great challenge. In this study, we report a new gene delivery vector based on dendrimer-entrapped gold nanoparticles (Au DENPs) with significantly higher gene transfection efficiency than that of dendrimers without AuNPs entrapped. Amine-terminated generation 5 poly(amidoamine) (PAMAM) dendrimers (G5.NH(2)) were utilized as templates to synthesize AuNPs with different Au atom/dendrimer molar ratios (25:1, 50:1, 75:1, and 100:1, respectively). The formed Au DENPs were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios and compositions of Au DENPs were characterized by gel retardation assay, light scattering, zeta potential measurements, and atomic force microscopic imaging. We show that the Au DENPs can effectively compact the pDNA, allowing for highly efficient gene transfection into the selected cell lines as demonstrated by both Luc assay and fluorescence microscopic imaging of the EGFP expression. The transfection efficiency of Au DENPs with Au atom/dendrimer molar ratio of 25:1 was at least 100 times higher than that of G5.NH(2) dendrimers without AuNPs entrapped at the N/P ratio of 2.5:1. The higher gene transfection efficiency of Au DENPs is primarily due to the fact that the entrapment of AuNPs helps preserve the 3-dimensional spherical morphology of dendrimers, allowing for more efficient interaction between dendrimers and DNA. With the less cytotoxicity than that of G5.NH(2) dendrimers demonstrated by thiazoyl blue tetrazolium bromide assay and higher gene transfection efficiency, it is expected that Au DENPs may be used as a new gene delivery vector for highly efficient transfection of different genes for various biomedical applications.
- Prodrug Systems (II): a perspective of Polymer-based Doxorubicin Prodrug systems towards chemotherapyPublication . Wang, Zhao; Olim, Filipe; Sun, Jingjing; Neves, Ana Rute; Mendes, Fátima; Tomás, Helena; Sheng, RuilongUtilizing biocompatible polymers as platforms to covalently conjugate with chemotherapeutics to construct polymer-based prodrugs and their nano drug delivery systems has attracted great attention in recent years. This perspective reviewed state-of-the-arts for polymer-based doxorubicin prodrugs and the related nanodelivery systems, including: (1) pH-responsive polymer-doxorubicin prodrugs/conjugates; (2) pH/redox dual responsive prodrugs/conjugates; (3) reactive oxygen species/hypoxia-responsive polymer-doxorubicin prodrugs; (4) tumor receptor targeting polymer prodrugs; (5) enzyme-responsive polymer-doxorubicin prodrugs. Finally, possible future perspectives were also stated and discussed.
- Prodrug Systems (I): Lipid-based Doxorubicin Prodrugs and their nanodelivery systemsPublication . Olim, Filipe; Neves, Ana Rute; Wang, Zhao; Sun, Jingjing; Tomás, Helena; Sheng, RuilongUsing natural lipids to covalently connect with antitumor agents to construct lipid-based molecular prodrugs and their nanosystems is a promising research frontier for sustainable medicinal chemistry, nanobiotechnology and tumor chemotherapy. This paper reviewed recent progress of lipid-based doxorubicin (molecular) prodrugs and their nanodelivery systems, including lipid-doxorubicin prodrugs, stimuli-responsive lipid-doxorubicin prodrugs, and lipid-doxorubicin prodrug-based drug co-delivery nanosystems. Additionally, possible future research outlooks in this field were also discussed.
- A dual-analytes responsive fluorescent probe for discriminative detection of ClO− and N2H4 in living cellsPublication . Zhu, Beitong; Wu, Xiaoli; Rodrigues, João; Hu, Xichao; Sheng, Ruilong; Bao, Guang-MingHydrazine (N2H4) and ClO− are very harmful for public health, hence it is important and necessary to monitor them in living cells. Herein, we rationally designed and synthesized a dual-analytes responsive fluorescent sensor PTMQ for distinguishing detection of N2H4 and ClO−. PTMQ underwent N2H4-induced double bond cleavage, affording colorimetric and green fluorescence enhancement with good selectivity and a low detection limit (89 nM). On the other hand, PTMQ underwent ClO−-induced sulfur oxidation and displayed red fluorescence lighting-up response towards ClO− with good selectivity, rapid response (<0.2 min) and a low detection limit (58 nM). Moreover, PTMQ was successfully employed for in-situ imaging of N2H4 and ClO− in living cells
- Self‐assembly of cholesterol‐Doxorubicin and TPGS into Prodrug‐based nanoparticles with enhanced cellular uptake and Lysosome‐dependent pathway in breast cancer cellsPublication . Olim, Filipe; Neves, Ana Rute; Vieira, Mariana; Tomás, Helena; Sheng, RuilongDeveloping new easy-to-prepare functional drug delivery nanosystems with good storage stability, low hemotoxicity, as well as controllable drug delivery property, has attracted great attention in recent years. In this work, a cholesterol-based prodrug nanodelivery system is prepared by self-assembly of cholesterol-doxorubicin prodrug conjugates (Chol-Dox) and tocopherol polyethylene glycol succinate (TPGS) using thin-film hydration method. The Chol-Dox/TPGS assemblies (molar ratio 2:1, 1:1, and 1:2) are able to form nanoparticles with average hydrodynamic diameter of ≈140–214 nm, surface zeta potentials of ≈−24.2–−0.3 mV, and remarkable solution stability in 0.1 m PBS, 16 days). The Chol-Dox/TPGS assemblies show low hemotoxicity and different cytotoxicity profiles in breast cancer cells (MCF-7 and MDA-MB-231), which are largely dependent on the molar ratio of Chol-Dox and TPGS. The Chol-Dox/TPGS assemblies tend to enter into MCF-7 and MDA-MB-231 cells through non-Clathrin-mediated multiple endocytosis and lysosome-dependent uptake pathways, moreover, these nanoassemblies demonstrate lysosome-dependent intracellular localization, which is different from that of free DOX (nuclear localization). The results demonstrate that the Chol-Dox/TPGS assemblies are promising cholesterol-based prodrug nanomaterials for breast cancer chemotherapy. Practical Applications: This work demonstrates a lipid prodrug-based nanotherapeutic system. Herein the Chol-Dox/TPGS nanoassemblies could serve as promising and controllable cholesterol-based prodrug nanomaterials/nano-formulations for potential breast cancer chemotherapy.
- Polysaccharide-based nanomedicines for cancer immunotherapy: a reviewPublication . Zeng, Yujun; Xiang, Yufan; Sheng, Ruilong; Tomás, Helena; Rodrigues, João; Gu, Zhongwei; Zhang, Hu; Gong, Qiyong; Luo, KuiCancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.